Peripherally restricted μ-opioid receptor antagonists: a review

Two new opioid antagonists, methylnaltrexone and alvimopan, are currently in late-stage clinical trials. With limited ability to cross the blood-brain barrier due to polar chemical structures, they act as peripherally active μ-opioid receptor antagonists, reversing many of the undesired effects of opioids without affecting centrally mediated analgesia or precipitating withdrawal. One of the most common and troubling side effects of opioids is inhibition of gastrointestinal (GI) motility, which increases pain, decreases patient satisfaction, and delays hospital discharge following abdominal surgery. In this article, we review the effectiveness of these new agents, particularly with respect to GI function, in postoperative as well as chronic pain patients. We also consider several novel effects these drugs have in wound healing, cancer growth, and HIV infectivity.